Earlier work on this project has established the inhibitory influence of a substance present in hypothalamic tissue upon release of melanocyte-stimulating hormone (MSH) from the pituitary. We plan to continue to study the MSH-release inhibiting factor (MIF) and its interactions with other systems. The extra-pigmentary effects of MSH upon the central nervous system (CNS) will be further investigated. In particular, several effects will be studied in an attempt to better define the CNS effects of MSH, particularly now that its clinical effects have been observed in mentally retarded men. The thorough study should yield results applicable to other peptide-hormones. It appears from work done previously on this subject that a small peptide found in the hypothalamus with MIF actively has direct effects upon the brain which do not require the presence of the pituitary gland. This MIF tripeptide, Pro-Leu-Gly-NH2, is active in several systems which some investigators consider animal models of parkinsonism and mental depression and has been found in several clinical studies based on the animal work to alleviate the symptoms of Parkinson's disease. It is proposed to continue these investigations and determine the mechanism by which these effects are exerted upon the central nervous system.